title: SET-domain bacterial effectors target heterochromatin protein 1 to activate host rDNA transcription.
abstract: Transcription of rRNA genes (rDNAs) in the nucleolus is regulated by epigenetic chromatin modifications including histone H3 lysine (de)methylation. Here we show that LegAS4, a Legionella pneumophila type IV secretion system (TFSS) effector, is targeted to specific rDNA chromatin regions in the host nucleolus. LegAS4 promotes rDNA transcription, through its SET-domain (named after Drosophila Su(var)3-9, enhancer of zeste [E(z)], and trithorax [trx]) histone lysine methyltransferase (HKMTase) activity. LegAS4's association with rDNA chromatin is mediated by interaction with host HP1α/γ. L. pneumophila infection potently activates rDNA transcription in a TFSS-dependent manner. Other bacteria, including Bordetella bronchiseptica and Burkholderia thailandensis, also harbour nucleolus-localized LegAS4-like HKMTase effectors. The B. thailandensis type III effector BtSET promotes H3K4 methylation of rDNA chromatin, contributing to infection-induced rDNA transcription and bacterial intracellular replication. Thus, activation of host rDNA transcription might be a general bacterial virulence strategy.
authors.affiliation: State Key Laboratory for Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention Beijing, 102206, China. liting@caiq.gov.cn
authors.forename: Ting
authors.initials: T
authors.lastname: Li
authors.forename: Qiuhe
authors.initials: Q
authors.lastname: Lu
authors.forename: Guolun
authors.initials: G
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.forename: Huanwei
authors.initials: H
authors.lastname: Huang
authors.forename: Tao
authors.initials: T
authors.lastname: Cai
authors.forename: Biao
authors.initials: B
authors.lastname: Kan
authors.forename: Jianning
authors.initials: J
authors.lastname: Ge
authors.forename: Feng
authors.initials: F
authors.lastname: Shao
mesh_terms: D000595:Amino Acid Sequence; D016950:Bordetella bronchiseptica / Q000235:genetics / Q000472:pathogenicity; D019117:Burkholderia / Q000235:genetics / Q000472:pathogenicity; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D000090266:Chromobox Protein Homolog 5; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics* / Q000378:metabolism; D004275:DNA, Ribosomal / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D006367:HeLa Cells; D006657:Histones / Q000235:genetics / Q000378:metabolism; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D016952:Legionella pneumophila / Q000235:genetics / Q000472:pathogenicity*; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic; D020298:U937 Cells
chemical_list: C518294:CBX3 protein, human; C000715594:CBX5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D004275:DNA, Ribosomal; D006657:Histones; D000090266:Chromobox Protein Homolog 5